The purpose of this funding opportunity announcement
(FOA), issued by NINDS, is to invite applications to participate as a Data
Coordinating Center in the Network for Excellence in Neuroscience Clinical
Trials. This clinical research network will develop and conduct multiple,
scientifically sound, possibly biomarker-informed exploratory clinical trials
evaluating the most promising therapies, whether from academic, foundation or
industry discoveries. Examples include Phase 2 clinical trials and clinical
research studies aimed at validating biomarkers and clinical outcomes in
preparation for clinical trials.

The network will provide a robust, standardized, and
accessible infrastructure to facilitate rapid development and implementation
of protocols in neurological disorders affecting adult and/or pediatric
populations.

While the network will not be specific to one disease, it
will have the capacity to coordinate a cadre of specialist investigators to
implement studies efficiently in response to disease-specific opportunities.

This FOA solicits applications for the Data Coordinating
Center (DCC). Separate FOAs solicit applications for the Clinical Sites and
the Clinical Coordinating Center (RFA-NS-008 and RFA-NS-009).

Key Dates

Posted Date

December 7, 2010

Letter of Intent Due Date

February 11, 2011

Application Due Date(s)

March 11, 2011

AIDS Application Due Date(s)

Not Applicable.

Scientific Merit Review

May/June 2011

Advisory Council Review

August 2011

Earliest Start Date(s)

September 2011

Expiration Date

March 12, 2011

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in
the PHS398
Application Guide except where instructed to do otherwise (in this FOA or
in a Notice from the NIH Guide for Grants and Contracts). Conformance
to all requirements (both in the Application Guide and the FOA) is
required and strictly enforced. While some links are provided, applicants must
read and follow all application instructions in the Application Guide as well
as any program-specific instructions noted in Section IV. When the program-specific
instructions deviate from those in the Application Guide, follow the
program-specific instructions. Applications that do not comply with
these instructions may be delayed or not accepted for review.

The purpose of this funding opportunity announcement (FOA),
issued by NINDS, is to invite applications to participate as a Data
Coordinating Center in the Network for Excellence in Neuroscience Clinical
Trials. This clinical research network will develop and conduct multiple,
scientifically sound, possibly biomarker-informed exploratory clinical trials
evaluating the most promising therapies, whether from academic, foundation or
industry discoveries. Examples include Phase 2 clinical trials and clinical
research studies aimed at validating biomarkers and clinical outcomes in
preparation for clinical trials.

The network will provide a robust, standardized, and
accessible infrastructure to facilitate rapid development and implementation of
protocols in neurological disorders affecting adult and/or pediatric
populations. While the network will not be specific to one disease, it will
have the capacity to coordinate a cadre of specialist investigators to
implement studies efficiently in response to disease-specific opportunities.

The network will include multiple Clinical Sites, one
Clinical Coordinating Center (CCC), and one Data Coordinating Center (DCC). The
network is designed to increase the efficiency of clinical trials, to
facilitate patient recruitment and retention, to increase the quality of
neuroscience clinical trials, and to enable public-private partnerships.

BACKGROUND

To translate recent, high quality neuroscience discoveries
into better treatments for people burdened by neurological disorders, efficient
clinical trials are needed. These trials require cooperation and coordination
among investigators, patients and industry partners. Clinical trial networks
can increase the efficiency of research by providing infrastructure,
centralized resources, and access to patients; however, with more than 400
neurological diseases falling under the auspices of NINDS, creating multiple
specialized research networks would not be feasible.

In the traditional model, a consortium of clinical sites is
created for each new multi-center trial. This causes redundancy and delays
because infrastructure is duplicated. Protracted contract negotiations and
approvals at multiple Institutional Review Boards (IRBs) often cause further
delays. In addition, there may be loss of expertise as experienced research
coordinators move to other fields after a trial is completed. The objective of
the network is to increase the efficiency of clinical research through shared
infrastructure for NINDS clinical trials.

RESEARCH
OBJECTIVES

The network aims to share expertise and infrastructure
across diseases, to leverage research resources at clinical sites, and to
flexibly take advantage of clinical research opportunities as they arise in
different disease areas. Finite resources and – especially for rare diseases –
a small pool of potential participants limit the number of large, confirmatory
efficacy (Phase 3) trials that can be conducted at any given time. Therefore,
NINDS aims through the network to support exploratory trials that can provide
more rapid preliminary testing of new treatments.

The objective of the network is to streamline the
implementation of clinical research by using standardized master trial
agreements and infrastructure that utilizes a central IRB of record. While
NINDS has historically funded trials to test drugs already approved for other
indications, the network is designed to assure the broadest access to any new
therapies for patients by carrying out trials coming from partnerships between
NINDS and industry, foundations, or academia. These trials will be utilizing a
variety of the NIH agreement mechanisms (e.g., Cooperative Research and
Development Agreements [CRADAs]) that maximize industry participation and
support.

It is envisioned that the network will not be
"idle" at any time. During the start-up period, as well as during
periods of time when new network projects will not take up the entire network
capacity, the Clinical Site coordinators and principal investigators will
improve the quality and facilitate the implementation of clinical trials at
their sites, by offering their support to ongoing NINDS-funded trials and
enhancing patient recruitment and retention. The CCC will track site
performance as it relates to ongoing NINDS-funded trials.

RESEARCH
APPROACHES

Shared Network Infrastructure

This FOA encourages applications for funding of
infrastructure for data and statistical coordination. The additional
project-specific funds to support the implementation of network protocols will
be part of future awards.

Responsibilities of the DCC include the following:

The DCC will provide full statistical support from trial
conception, design, implementation (including but not limited to
randomization), to interim analysis, final analysis, and publication;

The DCC will also provide full data management support from conception,
planning, building a trial database with user-friendly, web-based data entry,
data quality control, data monitoring, preparation of reports for the Data and
Safety Monitoring Board (DSMB) and analyses, data lock, data cleaning, and
preparing datasets for submission to an NINDS data repository;

The DCC will provide support for web-based communication and
access to study-wide information (e.g., protocol amendments), as well as for a
public website for each trial to promote outreach and recruitment.

Network Projects

Over the 7-year project period, the network will conduct
approximately 5-7 clinical research projects, and will promote the
implementation of ongoing NINDS-funded clinical trials. The exact number of
protocols supported in the 7-year program will depend on the nature and extent
of the investigations proposed and the availability of funds.

To ensure that the network is efficiently using resources
from its inception, a short-term clinical research project will begin soon after
the network has been established. It is anticipated that this first project
will be a biomarker validation study for spinal muscular atrophy (SMA). A separate
future FOA will solicit applications for this SMA protocol. Additional trials
will be selected from project proposals from industry and academic
investigators submitted in response to a second, future FOA that will solicit
applications for network Phase 2 clinical trials to be implemented through the
network. It is anticipated that at least one of the total trials conducted will
be targeted to children.

Following a second level of review by the NINDS advisory
council, NINDS will select protocols to be fully developed by a protocol lead
team consisting of the Project Director/Principal Investigator (PD/PI,
disease-experts as co-investigators, and network representatives.

The final protocol for each selected study will be approved
after technical review by a Protocol Review Committee. A subset or all of the
Clinical Sites will then be invited to participate in a given project and will
have the option to accept or decline, depending on their capacity, interest,
and patient population relevant to the specific protocol. It is also possible
that non-network sites may be added ad-hoc for a specific project, for their
expertise and patient population to complement network sites.

RESEARCH
TOPICS

The Data Coordinating Center' Scope of Work includes,
but is not limited to:

Promoting standardization of data collection across trials,
including using the NINDS Common Data Elements (CDE), when available, or helping
develop common data elements by working with NINDS on submitting data elements
and meta-information for use in the CDE initiative. (see http://www.commondataelements.ninds.nih.gov for more details);

Working with the CCC to report and track trial status in terms of
enrollment and retention;

Transferring data to statistician and others for interim analysis
as needed, and at the end of follow-up, cleaning and closing-out the database.

2) Data
Quality Assurance

Overseeing data quality control, including but not limited to
regular data queries and data monitoring and cleaning to assure data
completeness and quality.

3) Data
Sharing

Supporting and promoting data sharing after trial completion by
preparing a final, limited personal health information or de-identified data
set in a format appropriate for data sharing, for submission to a secure data
repository after publication of the primary study results or after 18 months,
whichever comes first.

4) Communication

Working with the CCC and Clinical Sites to support study
communication, including, but not limited to an investigator communication
platform/website where the study documents, the protocol and amendments, the manual
of procedures, and the other study communications are stored;

Working with the CCC to ensure that the trial status and results
are posted on clinicaltrials.gov, as required;

Working with the CCC, clinical sites, and network project teams, to
create a public website as platform for recruitment and outreach efforts for
all network projects.

5) Monitoring

Identifying an experienced clinical monitor to conduct at least
annual site visits to monitor the quality of record keeping, source
documentation and the accuracy of data entry.

6) Statistical
Support

Identifying at least one experienced statistician, with a
documented track record in successfully designing and implementing clinical
trials: expertise in Phase 2 trials is required, and expertise in efficient
trial designs and trials in small populations is preferred;

Providing statistical input to potential network project
applicants at the request of NINDS in the conceptual, pre-submission phase;

Providing statistical expertise to the trial design in the
planning and protocol development phase;

Collaborating with the clinical investigators in the preparation
of presentations of primary and secondary publications;

Providing additional analyses at the request of the DSMB, the
FDA, or the NINDS;

For network trial applicants who already have an established and
successful working relationship with a statistician in the field of the
application, the NINDS may allow for his/her participation; this
project-specific statistician will have to be willing to work closely with the
DCC team and DCC lead statistician in a collaborative manner and under a
pre-specified statistical leadership plan.

7) Collaborating
with Other Network Components

The DCC PD/PI will be a member of the Steering Committee (SC) and
will be serving as DCC member on network lead protocol development working
groups. The network SC is the main governing body of the network, and works
with the NINDS to oversee the implementation of all network protocols. The DCC PD/PI
and team will be working with PIs of potential new projects during the
conceptual phase, and with PIs of network projects selected for funding during
the protocol development and planning phase. The DCC PD/PI and team will be working
with the project specific SC during the implementation and analysis/publication
phase. The DCC PD/PI will be responsible for data quality.

The DCC will be working closely with the CCC in a collaborative
and interactive manner. The DCC and CCC – once selected for potential funding –
will submit to the NINDS jointly their respective SOPs, revised from the
version originally submitted with their applications, based on their jointly developed
collaboration plan. They will also submit a scope of work document detailing
the division of tasks and responsibilities within their proposed budget. Before
the award is made, the NINDS will review for approval the joint SOP and scope
of work documents. It is essential that the tasks required in planning and
executing a complex, multi-centered trial be clearly defined, and that the
responsibilities of the collaborators (including DCC and CCC) be delineated.
It is required that the joint DCC and CCC SOPs and scope of work document show
excellent and seamless communication and coordination and reflect an in-depth
understanding of the overall operational conduct of a complex, multi-center
trial.

Network Structure and Management

The NINDS Network of Excellence in Neuroscience Trials will
include: one Data Coordinating Center (DCC), one Clinical Coordinating Center
(CCC), and up to 25 Clinical Sites.

NINDS will be responsible for organizing and providing overall
support for the network. The NINDS Office of Clinical Research staff and the
NINDS Office of Grants Management will be responsible for the overall
management of the network. In addition to regular grant stewardship, an NINDS
Project Scientist will be involved substantially with the awardees as NINDS
partner, consistent with the Cooperative Agreement mechanism. The NINDS will
appoint a Scientific Advisory Board (SAB). The SAB is an external group of
experts who will review the network program and advise the network
investigators and the NINDS.

A Steering Committee (SC) composed of three principal
investigators representing the Clinical Sites, the DCC PI, the CCC PI, plus the
PIs of active network projects and the NINDS Project Scientist will be the main
governing body of the network. NINDS will appoint a SC Chair to preside over SC
meetings and serve as the SC representative to the SAB.

All major scientific decisions will be determined by majority
vote of the SC;

Each SC member will have one vote; the SC Chair will cast a vote
in case of a tie;

The protocol lead PIs of approved network protocols will become SC
members for the duration of the project they are leading;

The initial three Clinical Site representative PIs will be
appointed by NINDS to the SC for a 2 to 3-year term;

The second slate of SC investigator-members will consist of the
highest overall enrolling investigator and two investigators elected by their
peer investigators to a 2-year term. For continuity, one of the three initial
SC investigator members will remain for 2 years, and two will remain for 3
years so that not all tenures expire at the same time;

It is anticipated that the SC will meet two times per month by
telephone conference call and at least three times per year by in-person
meetings;

The SC will have primary responsibility for network governance. SC
working groups will be established by the SC, on an as-needed basis, to perform
specific functions such as, for example:

Protocol planning and development;

Per-patient budget approval;

Publications.

The DCC will support protocol development and implementation with
regards to statistical design, data management, data quality assurance, and
analysis, as described above;

The CCC provides overall study coordination and quality
assurance, working closely with the DCC and the CSs. The CCC coordinates the
activities of the SC, develops and implements investigator and staff training
programs and meetings, oversees drug acquisition and distribution as needed,
works closely with the project-specific protocol development and SCs, supports
project investigators in IND submission and reporting to the FDA, conducts clinical
site visits, establishes and maintains standardized master trial agreements
with the network sites, distributes funding for network trial projects,
maintains regulatory documents and coordinates the central, federated IRB
process, supports outreach to patients and inclusion of patients in protocol
and recruitment plan development, provides editorial and meeting coordination
for manuscript preparation, and develops operational and publication guidelines
within the framework outlined in this RFA. See RFA-NS-11-009 for more details describing the responsibilities of the network CCC.

Section II. Award Information

Funding Instrument

This FOA will use the NIH U01 research Project Cooperative
Agreement award mechanism (U01). In the cooperative agreement mechanism, the
PD(s)/PI(s) retain(s) the primary responsibility and dominant role for
planning, directing, and executing the proposed project, with NIH staff being
substantially involved as a partner with the PD(s)/PI(s), as described under
the Section VI.2. Administrative Requirements, "Cooperative Agreement
Terms and Conditions of Award".

Application Types Allowed

New

The OER
Glossary and the PHS398 Application Guide provide details on these application
types.

Funds Available and Anticipated Number of Awards

The total amount of funding that NINDS expects to award
through this announcement is up to $13.2 Million.

The anticipated number of awards is one (1).

Although the financial plans of the IC provide support for
this program, awards pursuant to this funding opportunity are contingent upon
the availability of funds.

Award Budget

The expected direct cost amount for individual awards is
up to $1.25 Million annually for 7 years.

Facilities and Administrative (F&A) costs requested by
consortium participants are not included in the direct cost limitation. See NOT-OD-05-004.

NIH grants policies as described in the NIH Grants Policy
Statement will apply to the applications submitted and awards made in
response to this FOA.

Award Project Period

This is a one-time solicitation to fund the network for 7
years. Plans beyond the current funding period are undetermined.

NIH grants policies as
described in the NIH Grants
Policy Statement will apply to the
applications submitted and awards made in response to this FOA.

Section
III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions:

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions
are always encouraged to apply for NIH support as Public or Private
Institutions of Higher Education:

Non-domestic (non-U.S.) Entities (Foreign Organizations) are
not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Required Registrations

Applicant organizations must complete the following registrations
as described in the PHS398 Application Guide to be eligible to apply for or
receive an award. Applicants must have a valid Dun and Bradstreet Universal
Numbering System (DUNS) number in order to begin each of the following
registrations.

All Program Directors/Principal Investigators (PD/PIs) must
also work with their institutional officials to register with the eRA Commons
or ensure their existing eRA Commons account is affiliated with the eRA Commons
account of the applicant organization.

All registrations must be completed by the application due
date. Applicant organizations are strongly encouraged to start the registration
process at least four (4) weeks prior to the application due date.

Eligible Individuals (Project Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Project Director/Principal
Investigator (PD/PI) is invited to work with his/her organization to develop an
application for support. Individuals from underrepresented racial and ethnic
groups as well as individuals with disabilities are always encouraged to apply
for NIH support.

The PD/PI for the network Data Coordinating Center will be
an experienced statistician and clinical trial data management expert, with a
track record in successfully implementing the statistical and data aspects of multicenter
clinical trials. Institutions will be required to document commitment to the PD/PI
by providing departmental and institutional support letters, and are encouraged
to demonstrate support via other means (e.g., additional protected time,
departmental research leadership position, facilities, space, or resources for
the PD/PI).

Only one DCC application per institution (normally
identified by having a unique DUNS number or NIH IPF number) is allowed.
However, applicants may apply for an award for the CCC or Clinical Site
(separate FOAs) as well as for an award under this FOA.

Awards for a CCC and a DCC will not be made to the same
Principal Investigator, to ensure that data analyses and data acquisition are
performed independently.

Awards for a DCC and a Clinical Site may be made to the
same institution.

However, it is preferred that the DCC and a Clinical
Site at the same institution be led by separate investigators, to ensure that
the DCC activities as well as the local Clinical Site activities receive full attention.

This section contains other eligibility criteria, if
applicable (e.g., if entities have violated a particular statute).

NIH will not accept any application in response to this FOA
that is essentially the same as one currently pending initial peer review
unless the applicant withdraws the pending application. NIH will not accept any
application that is essentially the same as one already reviewed. Resubmission applications are not permitted in response to this FOA.

Renewal applications are not permitted in
response to this FOA.

Section IV. Application and
Submission Information

1. Address to Request Application Package

Applicants are required to prepare applications according to
the current PHS 398 application forms in accordance with the PHS 398
Application Guide.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in
the PHS398
Application Guide, except where instructed in this funding opportunity
announcement to do otherwise. Conformance to the requirements in the
Application Guide is required and strictly enforced. Applications that are out
of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

A letter of intent is required.

By the date listed in Part 1. Overview
Information, prospective applicants are asked to submit a letter of intent
that includes the following information:

Descriptive title of proposed research;
Name, address, and telephone number of
the PI;
Names of other key personnel;
Participating institutions;
Number and title of this funding
opportunity.

Pre-Application Meeting: The NINDS anticipates holding a
technical assistance meeting in January 2011 (now December 17, 2010 per NOT-NS-11-005), through a teleconference to which
all interested prospective applicants are invited. Program and review staff
will make presentations that explain their goals and objectives for the NEXT
Initiative and answer questions from the attendees. Prospective applicants are
urged to monitor the NIH Guide for Grants and Contracts regarding a Notice for
the date and time of the meeting (http://grants.nih.gov/grants/guide/index.html).

Application Submission

Applications must be prepared using the PHS 398 research
grant application forms and instructions for preparing a research grant
application. Submit a signed, typewritten original of the application, including
the checklist, and three signed photocopies in one package to:

All page limitations described in the PHS398 Application
Guide must be followed, with the following exceptions or additional
requirements:

Research Strategy section is limited to 30 pages. Applications received
that exceed these page limitations will not be reviewed.

Research Plan

All instructions in the PHS398 Application Guide must be
followed, with the following additional instructions:

Applications
should include the following information in the relevant subsections:

1)
Leadership Plan

The PD/PI should describe in the Approach section of
the Research Strategy how clinical trials and research will be strategically
supported by the network Data Coordinating Center PD/PI and staff, and how the
data management and statistical team will be directed.

2)
Collaboration and Communications Plan

In the relevant sections of the Biosketch, Resources/Facilities
and the Research Strategy or (where applicable), in the multiple PD/PI Leadership
Plan, applicants should state their general support of collaborative research
and their willingness to participate in a collaborative and interactive manner
with the Clinical Sites, the Clinical Coordinating Center, and NINDS and its
partners in all aspects of the network program. Applicants should describe
their communications plan with the CCC and Clinical Sites within the network.
Applicants are encouraged to describe any special expertise or unique strengths
they can offer to the collaborative effort (e.g., established database tools, hardware,
software, quality control tools, monitoring expertise, team leadership and
training, communications platforms, website design and management).

3)
Data Management, Quality Assurance and Monitoring Plan

Based on the tasks outlined above, the PD/PI should
describe in the Approach section of the Research Strategy, how the data
management, quality assurance and monitoring programs for network projects will
be supported, building on existing strengths. A data management system should:

Collect data in a user-friendly manner, with a user interface
directed at the experience and knowledge of users (rather than that of
programmers, data managers or statisticians);

Collect data in a manner appropriate to the source of data (i.e.,
data collected by people should be entered by people, data generated by
machines should be imported from the machine, data generated in a lab should be
entered by the lab, etc.);

Integrate data from disparate sources seamlessly;

Validate data as thoroughly as possible on collection and/or
entry;

Validate data completely, on an ongoing basis;

Have a rigorous error and query resolution process, which
monitors data quality throughout the collection process;

Allow for the easy dissemination of data to statisticians and
other analysts, in a variety of tab delimited formats;

Allow for the easy production of regular reports on trial status
and progress;

Have graduated, role-based security, which permits varying degrees
of access to data based on an individual’s role in the study;

Protect any personal health information (PHI) collected from
unauthorized access, and create a log of all authorized access;

Assemble all study data in a well-documented central store, to
facilitate data sharing and dissemination.

4)
Statistical Support Plan

Based on the outline above, the PD/PI should describe
in the Approach section of the Research Strategy, how all statistical aspects
of trials from the pre-application conceptual phase, the planning phase, the
implementation phase and the analysis and publication phase will be supported.
It is anticipated that the DCC will provide full statistical support for all network
projects. However, the PD/PI should briefly describe how in the alternative
scenario of a non-DCC statistician this statistician would be integrated in network
DCC operations of their project. Under the alternative scenario, the project
statistician leads the statistical design, analysis plans, and the final
analysis for publication, remaining blinded during the course of the trial.
The DCC statistician leads the data management and preparation of unblended
reports and analyses. In the Conceptual and Planning phases, both statisticians
will work together to ensure the design is suitable for implementation through
the network. The applicant should outline their expertise in exploratory
clinical trials and adaptive designs.

5)
Plan to Increase Data Sharing Opportunities

According to the goals and tasks outlined above, the PD/PI
should describe in the Approach section of the Research Strategy or in the Resource
Sharing Plan section how standardization of protocols, data collection and data
collection instruments will be promoted, including the integration of NINDS
common data elements, if applicable. The PD/PI should describe how datasets of
completed trials will be submitted for data sharing to an NINDS repository,
using data exchange standards.

6)
Trial Start-up and Participant Recruitment

Participation in the network will be a complex and
time-consuming undertaking. Therefore, in the Research Strategy under
Preliminary Data/Approach section, the applicant should include a description
of current and up to five of the most recently completed trials that were
coordinated by the DCC, along with a detailed record indicating the following,
in a table or bulleted format:

The start-up time for each trial in terms of establishing a
database and other tools (including CRFs, randomization mechanism)

Time from last patient last visit to database lock

Time from database lock to final primary analysis

In addition, the application should include the
following information:

A description of data management system/software the applicant
uses currently or proposes to use for this network should be provided in the
Resources/Facilities section of the application.

A description of data sharing procedures.

Published manuscripts that highlight recently coordinated trials
should be referenced in the application in the biosketch or in the literature
cited section of the application.

7)
Project Management and Coordination Plan

The application should include, in the Research
Strategy section, the SOPs, with key documents (e.g., Conflict of Interest
policy) used by the DCC in the implementation of multi-center clinical trials,
included, but not limited to SOPs describing database access, data quality
control, data queries with audit trails, etc.

Resource Sharing Plan

Individuals are required to comply with the
instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model
Organisms, and Genome Wide Association Studies (GWAS) as provided in the PHS398
Application Guide.

Appendix

Do not use the appendix to circumvent page limits. Follow
all instructions for the Appendix (please note all format requirements) as
described in the PHS398 Application Guide.

In accordance with the NIH policy on appendix materials (NOT-OD-07-018),
when a free, online, publicly available journal
link in not available, applicants should provide up to 3 manuscripts
either accepted for publication or in press that highlight recently coordinated
trials.

Applications must be received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not
be reviewed..

Upon receipt, applications will be evaluated for
completeness by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Links with NIH Resource Centers

Applications from institutions that have a General Clinical
research Center (GCRC) or Clinical and Translational Science Award (CTSA) funded
by the NIH National Center for Research Resources should identify in the Resources/Facilities
section, the resources that could be available to support the proposed network DCC,
commenting particularly on those aspects that will enhance their programmatic
and scientific efficiency. In such a case, a description of the GCRC or CTSA
and how the applicant proposes interacting with it should be included, as well
as letter of agreement (included in the Letters of Support section of the
application) from either the GCRC/CTSA Program Director or PI. Having a GCRC
or CTSA at the institution is not a requirement for application.

Budget

A detailed budget for the Data Coordinating Center
should be presented. The budget must include all activities delineated in the
list of DCC responsibilities included in this FOA.

All activities related to coordinating 5-7 clinical
research studies should be budgeted, including:

Conceptual activities;

Planning activities;

Start-up activities;

Randomization support;

Implementation activities;

Close-out phase activities;

Participation in investigator meetings, SC and other leadership
committee functions;

Site monitoring;

Communication, documentation and reporting;

Support of study drug management.

The PD/PI must be available to attend all network
investigator meetings, which may include conference calls twice a month and
in-person meetings at least three times each year.

The budget should also include travel costs for
approximately three trips each year for three team members to attend SC
meetings in Bethesda, MD, and other travel related to network operations
(including at least one visit per site and funding period).

The total should not exceed $1.25 Million direct costs per
year in years 1-7 (all of which will be 12-month project years). The release
of funds will be milestone-driven, according to milestones pre-specified in the
Notice of Grant Award. Facilities and administrative costs requested by
consortium participants are not included in the direct cost limitation (see
NOT-OD-05-004).

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review
Information

1. Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

Overall Impact

Reviewers will provide an overall impact/priority score to
reflect their assessment of the likelihood for the project to exert a
sustained, powerful influence on the research field(s) involved, in consideration
of the following review criteria and additional review criteria (as applicable
for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field?

Investigator(s)

Are the PD/PIs, collaborators, and other researchers
well suited to the project? If Early Stage Investigators or New Investigators,
or in the early stages of independent careers, do they have appropriate
experience and training? If established, have they demonstrated an ongoing
record of accomplishments that have advanced their field(s)? If the project is
collaborative or multi-PD/PI, do the investigators have complementary and
integrated expertise; are their leadership approach, governance and
organizational structure appropriate for the project?

Does the PD/PI have a track record of working collaboratively?

Does the PD/PI have a track record in successfully designing and
implementing the statistical and data management aspects of multicenter
clinical trials?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success presented?
If the project is in the early stages of development, will the strategy
establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements?

Does the institution show commitment to the PD/PI by providing
departmental and institutional support letters? The institutions are
encouraged to demonstrate support via other means (e.g., additional protected
time, departmental research leadership position, facilities, space, or
resources for the PD/PI).

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact/priority score, but will
not give separate scores for these items.

Do the investigators provide consistent evidence for
collaborative leadership in statistical and data coordination of multicenter
trials, and is there evidence of experience in and willingness to participate
appropriately in a collaborative program as described in this FOA?

Does the investigator have a successful track record in trial statistical
and data coordination?

Are interactions/communications between the DCC and the CCC,
clinical sites and the community clearly described and creatively optimized?

Are the investigators likely to carry-out the key tasks in a
timely manner, including, but not limited to establishing the database, data
cleaning, analysis, and data sharing?

Protections for Human Subjects

For research that involves human subjects but does not
involve one of the six categories of research that are exempt under 45 CFR Part
46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research,
the committee will evaluate the proposed plans for inclusion of minorities and
members of both genders, as well as the inclusion of children. For additional
information on review of the Inclusion section, please refer to the Human
Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the
following five points: 1) proposed use of the animals, and species, strains,
ages, sex, and numbers to be used; 2) justifications for the use of animals and
for the appropriateness of the species and numbers proposed; 3) adequacy of
veterinary care; 4) procedures for limiting discomfort, distress, pain and
injury to that which is unavoidable in the conduct of scientifically sound
research including the use of analgesic, anesthetic, and tranquilizing drugs
and/or comfortable restraining devices; and 5) methods of euthanasia and reason
for selection if not consistent with the AVMA Guidelines on Euthanasia. For
additional information on review of the Vertebrate Animals section, please
refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable.

Renewals

Not Applicable.

Revisions

Not Applicable.

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact/priority score.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will consider whether the budget and the
requested period of support are fully justified and reasonable in relation to
the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) convened by the NINDS Scientific Review Branch (assignments will be shown in the eRA Commons), in
accordance with NIH peer
review policy and procedures, using the stated review
criteria.

As part of the scientific peer review, all applications will:

Undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review), will be discussed and assigned an overall
impact/priority score.

Receive a written critique.

Applications will be assigned on the basis of established
PHS referral guidelines to the appropriate NIH Institute or Center and will
compete for available funds with all other recommended applications submitted in response to this FOA . Following initial peer review, recommended applications
will receive a second level of review by the National Advisory Neurological Disorders and Stroke Council.

For this particular announcement, the following will be
considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Track record and willingness to collaborate with other clinical
trial experts and clinical researchers;

Ability to begin operations immediately;

Willingness, and evidence of potential, to participate in all
aspects of the network program, including protocol development and other SC
working groups, and participation in teleconferences and in-person meetings;

Willingness to work collaboratively and strong track record of
successful data and statistical coordination and collaboration in large, multicenter
research teams;

Agreement to accept the Cooperative Agreement Terms and
Conditions of Award delineated in this FOA (see Section VI.2.A);

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the
PD/PI will be able to access his or her Summary Statement (written critique)
via the eRA
Commons.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH Grants
Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

The following special terms of award are in addition to, and
not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB)
administrative guidelines, U.S. Department of Health and Human Services (DHHS)
grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is
applicable when State and local Governments are eligible to apply), and other
HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the
cooperative agreement, an "assistance" mechanism (rather than an
"acquisition" mechanism), in which substantial NIH programmatic
involvement with the awardees is anticipated during the performance of the
activities. Under the cooperative agreement, the NIH purpose is to support and
stimulate the recipients' activities by involvement in and otherwise working
jointly with the award recipients in a partnership role; it is not to assume
direction, prime responsibility, or a dominant role in the activities.
Consistent with this concept, the dominant role and prime responsibility
resides with the awardees for the project as a whole, although specific tasks
and activities may be shared among the awardees and the NIH as defined below.

The DCC PD(s)/PI(s) will have the primary responsibility for:

Coordinating
all aspects of data collection and management for network research protocols,
including reporting to the NINDS, CCC, DSMB, and clinicaltrials.gov.

Awardees will retain custody of and have
primary rights to the data and software developed under these awards, subject
to Government rights of access consistent with current DHHS, PHS, and NIH
policies.

NIH staff have substantial programmatic involvement that
is above and beyond the normal stewardship role in awards, as described below:

The NINDS staff working with the network investigators will
develop performance milestones for the DCC. Failure to meet the agreed upon
milestones may result in reduced funding or early termination of the
cooperative agreement.

An NINDS Project Scientist will have substantial programmatic
involvement that is above and beyond the normal stewardship role in awards.

An agency program official
or IC program director will be responsible for the normal scientific and
programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

A SC composed of three Clinical Site PIs representing the
Clinical Sites, the DCC PD/PI, the CCC PD/PI, plus the PD/PIs of active network
projects and the NINDS Project Scientist will be the main governing body of the
network. NINDS will appoint a SC Chair.

The DCC PD/PI and other key staff are expected to participate in
all network teleconferences and investigator meetings. They are also expected
to serve on SC working groups established on an as-needed basis to develop and
oversee specific protocols, and to provide in-depth evaluation and
recommendations on such issues as publications/presentations, protocol
implementation, quality control, conflict of interest, and others.

Each full member will have one vote. Awardees will be
required to accept and implement policies approved by the SC.

Dispute Resolution:

Any disagreements that may arise in scientific or
programmatic matters (within the scope of the award) between award recipients
and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel
composed of three members will be convened. It will have three members: a
designee of the Steering Committee chosen without NIH staff voting, one NIH
designee, and a third designee with expertise in the relevant area who is
chosen by the other two; in the case of individual disagreement, the first
member may be chosen by the individual awardee. This special dispute resolution
procedure does not alter the awardee's right to appeal an adverse action that
is otherwise appealable in accordance with PHS regulation 42 CFR Part 50,
Subpart D and DHHS regulation 45 CFR Part 16.

A final progress report, invention
statement, and Financial Status Report are required when an award is
relinquished when a recipient changes institutions or when an award is
terminated.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.FSRS.gov on all subawards over $25,000. See
the NIH Grants Policy Statement for additional information on this reporting
requirement.

Section VII.
Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and
under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.